Primary hepatocellular carcinoma (hereinafter may be referred to as “liver cancer”) most often appears after progression of chronic hepatitis to cirrhosis. Many viral hepatitis and cirrhosis patients have been recognized, and, in recent years, incidence of liver cancer has been increasing. Liver cancer has been treated with, for example, hepatectomy, percutaneous local therapy (e.g., radiofrequency ablation therapy or ethanol injection therapy), transcatheter hepatic arterial embolization (TAE), continuous arterial infusion chemotherapy, or radiation therapy.
Liver cancer therapy is selected in consideration of the distribution and size of cancerous cells, and as well the underlying hepatic disorder (hepatitis or cirrhosis). Even when liver cancer patients are treated with a highly radical therapy, incidence of post-treatment intrahepatic ectopic recurrence is as high as 10 to 30% per year. Such post-treatment recurrence leads to poor prognosis of cancer-bearing patients. In consideration of such a high ectopic recurrence rate, patients who have undergone liver cancer treatment are followed up with frequent imaging or tests employing tumor markers.
Tumor markers which have conventionally been employed for liver cancer diagnosis include α-fetoprotein (AFP), α-fetoprotein lectin fraction (L3 fraction), and PIVKA-II. Such a tumor marker is fairly useful for liver cancer diagnosis, evaluation of therapeutic effect, and diagnosis of post-treatment recurrence in a high-risk patient with, for example, viral hepatitis or cirrhosis, but the tumor marker is often false-positive or false-negative. Therefore, clinically, diagnosis employing such a tumor marker is performed in combination with another imaging technique (e.g., abdominal ultrasound examination or CT scan), or through periodical analysis. A tumor marker which can evaluate the risk of liver cancer recurrence in background liver tissue immediately after treatment could provide advantages in that, for example, recurrence of liver cancer can be detected early, a more radical therapy causing no impairment of background liver disorder can be carried out, and load due to frequent examination can be reduced in patients with low recurrence risk. Therefore, demand has arisen for a diagnostic marker which is useful for prognosing the posttreatment recurrence of liver cancer.
A glypican family has been reported to be present, as a new family of heparan sulfate proteoglycan, on the surfaces of cells. As has been reported so far, the glypican family includes six glypican members (glypican-1, glypican-2, glypican-3, glypican-4, glypican-5, and glypican-6). The glypican family members have a core protein of uniform size (about 60 kDa), share a specific and well-retained cysteine arrangement, and are bound to the cell membrane by means of a glycosylphosphatidylinositol (GPI) anchor.
Glypican-3 (GPC3) has been known to be closely related to developmental cell division or control of cell division patterns. As has also been known, the GPC3 gene is highly expressed in liver cancer cells, and may be suitable for employment as a hepatocellular carcinoma marker. In addition, Patent Documents 1 and 2 have already disclosed a method for diagnosing cancer through measurement of GPC3. However, the manner in which GPC3 level changes after liver cancer treatment has never been known, nor has establishment of a therapeutic strategy through analysis of change in GPC3 level.
Patent Document 1: International Publication WO 03/100429 pamphlet
Patent Document 2: International Publication WO 2004/018667 pamphlet